방사선의학 웹진

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Abstract
Background: Radioresistance is a major clinical challenge in cancer treatment, as it reduces the effectiveness of radiation therapy (RT). While advances in radiation delivery have enabled the clinical use of high-dose hypofractionated RT, its impact on radioresistant tumors remains unclear. This study aimed to compare the effects of single high-dose RT with conventional fractionated RT on radioresistant breast cancer cells and explore the underlying mechanisms.

Methods: Radioresistant cell lines were previously established by exposing SK-BR-3 and MCF-7 cells to 48 Gy and 70 Gy of radiation, respectively, in multiple fractions. We compared the effects of 2 Gy × 5 and 7 Gy × 1 fractions on these cells using clonogenic survival assays and western blot analysis. In vivo antitumor effects were assessed in SR tumor-bearing BALB/c mice irradiated with either 2 Gy × 5 or 7 Gy × 1 fractions.

Results: 7 Gy x1 was more efficient at killing radioresistant breast cancer cells than 2 Gy x5. Furthermore, the 7 Gy x1 fraction produced higher levels of reactive oxygen species (ROS) and decreased the expression of radioresistance factors such as p-STAT3, ACSL4, FOXM1, RAD51, Bcl-xL, and survivin. Consistent with the in vitro studies, the 7 Gy × 1 fraction also showed superior antitumor effects in SR tumor-bearing BALB/c mice.

Conclusions: Single high-dose RT offers superior advantages over conventional fractionated RT in regard to overcoming radioresistance, supporting its potential as a promising treatment for recurrent tumors.

Affiliations

Yun-Suk Kwon 1 2, Phuong Anh Nguyen 2, Hai Yen Dao 2, Hyunsoo Jang 3, Soyoung Kim 2
1Research Institute of Climate Change and Agriculture, National Institute of Horticultural and Herbal Science, Jeju, Jeju-do, Republic of Korea.
2Department of Pharmacology, College of Medicine, Dongguk University, Gyeongju, Gyeongsangbuk-do, Republic of Korea.
3Department of Radiation Oncology, Pohang St. Mary's Hospital, Pohang, Gyeongsangbuk-do, Republic of Korea.